ISSN 0214 - 9915 CODEN PSOTEG
Psicothema 2019, Vol. 31, No. 3, 239-245
doi: 10.7334/psicothema2019.27
Associations between experimental substance use, FAAH-gene
variations, impulsivity and sensation seeking
Evelio Huertas, José A. López-Moreno, Vanessa Fernández, Víctor Echeverry-Alzate, and Kora-M Bühler
Complutense University of Madrid
Abstract
Background: Experimental substance use among young people is related
to individual factors including personality traits such as impulsivity
and sensation seeking, and genetic variations such as single nucleotide
polymorphisms (SNPs) in the fatty acid amide hydrolase (FAAH) gene.
The objective of this study is to analyze the relationship between these
three sets of variables. Methods: Volunteer undergraduate students (N
= 861, 76% female, M = 20.7 years) completed an ad hoc questionnaire
on variables related to their consumption of alcohol, tobacco, cannabis,
synthetic drugs and cocaine. In addition, 591 of them completed the
Barratt Impulsiveness Scale-11 (BIS-11) and the Sensation Seeking
Scale-V (SSS-V). All participants were genotyped in FAAH C385A SNP
and its proxy variant rs12075550. Results: Consistent with previous data,
both impulsivity and sensation seeking were associated with most of the
variables related to experimental substance use. In addition, we found the
first evidence of an association between the rs12075550 SNP and some
of these consumption phenotypes. However, no significant association
was found between either of the two SNPs and impulsivity or sensation
seeking. Conclusions: The results highlight the importance of considering
both personality and genetic differences, together with contextual factors,
in the analysis of substance use.
Keywords: Experimental substance use, impulsivity, sensation seeking,
rs12075550, FAAH C385A.
Substance use disorders are common, complex disorders,
characterized by compulsive substance seeking and use despite
harmful consequences. The initiation of substance use takes place
mainly during adolescence (Plan Nacional sobre Drogas, 2018).
An early onset of substance use is associated with a significantly
greater risk of later developing a substance use disorder (Chen,
Storr, & Anthony, 2009).
Various risk factors for substance use initiation have been
identified, including multiple contextual and individual variables
(e.g. Blanco, Flórez-Salamanca, Secades-Villa, Wang, & Hasin,
Received: January 31, 2019 • Accepted: May 30, 2019
Corresponding author: Evelio Huertas
Facultad de Psicología
Complutense University of Madrid
28223 Pozuelo de Alarcón
e-mail: ehuertas@ucm.es
Copyright © 2019 Psicothema
www.psicothema.com
Resumen
Asociaciones entre el uso experimental de sustancias, variaciones del gen
FAAH, impulsividad y búsqueda de sensaciones. Antecedentes: el uso
experimental de sustancias en los jóvenes está relacionada con factores
individuales que incluyen rasgos de personalidad, como impulsividad o
búsqueda de sensaciones, y variaciones genéticas, como polimorfismos
de un solo nucleótido (SNPs) del gen amida hidrolasa de ácidos grasos
(FAAH). El objetivo de este estudio es analizar la relación entre estos tres
conjuntos de variables. Método: estudiantes universitarios voluntarios (N
= 861, 76% mujeres, M = 20,7 años) rellenaron un cuestionario ad hoc de
variables relacionadas con el consumo de alcohol, tabaco, cannabis, drogas
sintéticas y cocaína. Además, 591 de ellos rellenaron las escalas BIS-11 y
SSS-V. Se genotipó a todos ellos en SNP FAAH C385A y su variante proxy
rs12075550. Resultados: como se esperaba, la impulsividad y la búsqueda
de sensaciones estuvieron asociadas con la mayor parte de las variables
relativas al uso experimental de sustancias. Además, encontramos por
primera vez evidencia de una asociación entre rs12075550 y algunos de
estos fenotipos de consumo. Sin embargo, no encontramos asociaciones
significativas entre SNPs e impulsividad o búsqueda de sensaciones.
Conclusiones: los resultados resaltan la importancia de tener en cuenta
las diferencias genéticas y las de personalidad, junto con los factores
contextuales, al analizar el uso de sustancias.
Palabras clave: uso experimental de sustancias, impulsividad, búsqueda
de sensaciones, rs12075550, FAAH C385A.
2018), and both prevention and treatment strategies must take
into account all these factors (Becoña, 2018). Among individual
variables, personality traits like impulsivity and sensation seeking
seem to be particularly relevant. Impulsivity is a multidimensional
construct that can be broadly defined as a tendency toward rapid
and unplanned reactions without regard to the consequences of
these reactions (Stanford et al., 2009). Evidence indicates that
impulsivity acts as a determinant factor for substance use initiation
(e.g. Fernie et al., 2013; Mitchell & Potenza, 2014; Rømer-Thomsen
et al., 2018; Verges, Littlefield, Arriaza, & Alvarado, 2019) and that,
in turn, substance use increases subsequent impulsive behaviors
(de Wit, 2009). Sensation seeking can be defined as the tendency
of the individual to seek out varied, novel and intense experiences
and the willingness to take risks for the sake of such experiences
(Zuckerman, 1994). Several studies have linked sensation seeking
with substance use disorders and have even indicated that it is
one of its most powerful predictors (e.g. Ames, Zogg, & Stacy,
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 Evelio Huertas, José A. López-Moreno, Vanessa Fernández, Víctor Echeverry-Alzate, and Kora-M Bühler
2002; Evans-Polce, Schuler, Schulenberg, & Patrick, 2018; Jaffe
& Archer, 1987; Malmberg et al., 2012; Martínez-Loredo et al.,
2018). Nevertheless, other studies suggest that abnormal sensation
seeking values are more likely to be a consequence of substance
use than a preexisting vulnerability factor (Ersche, Turton,
Pradhan, Bullmore, & Robbins, 2010).
Beyond personality and related to it, genetic characteristics
play an important role in the development of substance use
disorders. Data indicate that there are a number of genes, each
with a small influence, that interact with each other and with
environmental factors, affecting substance use and the likelihood
of developing a substance use disorder (e.g. Gray & Squeglia,
2018; Meyers & Dick, 2010). The influence of genetic factors
on substance use appears to increase considerably from early
adolescence to young adulthood (Rose, Dick, Viken, & Kaprio,
2001). Among genetic variations related to substance use, single
nucleotide polymorphisms (SNPs) in the endocannabinoid system
may play a relevant role (see Bühler et al., 2015 for a review). The
endocannabinoid system is implicated in a variety of cognitive
and physiological processes including modulation of learning and
memory, as well as brain reward signaling, influencing therefore
vulnerability to substance use disorders (Parsons & Hurd, 2015).
Among the different components of the endocannabinoid system,
the fatty acid amide hydrolase enzyme (FAAH) has received
special attention. This enzyme is responsible for the degradation
of endocannabinoids and is encoded by its homonym gene FAAH
which presents a missense SNP (rs324420/C385A) that reduces
the expression and the activity of that enzyme, resulting in
increased anandamide levels (Chiang, Gerber, Sipe, & Cravatt,
2004; Dincheva et al., 2015). Several studies have shown an
association between FAAH C385A and different phenotypes
related to substance use (e.g. Bühler et al., 2014; Sloan et al.,
2018; Sipe, Chiang, Gerber, Beutler, & Cravatt, 2002), although
the studies as a whole have shown heterogeneous results (Bühler
et al., 2015).
The effects of FAAH C385A can depend on its interaction
with other SNPs. In this line, Flanagan, Gerber, Cadet, Beutler,
and Sipe (2006) revealed a haplotype which included FAAH
C385A and its proxy variant rs12075550 –D’ = 1, r = 0.1875 in
Caucasian individuals– (Michiela & Chanock, 2015). Rs12075550
is approximately 37 Kb from the C385A locus, in a non-coding
region near the FAAH gene, which is likely to affect activator
protein binding and expression of this gene (Boyle et al., 2012;
Veyrieras et al., 2008). However, there is a deep lack of information
about the influence of rs12075550 on human phenotypes, including
those related to substance use.
In addition to different consumption phenotypes, FAAH
C385A has been previously associated with impulsivity (Hariri et
al., 2009). However, Bidwell et al. (2013) did not find a significant
interaction of impulsivity and FAAH-gene variations (including
C385A but not rs12075550) to predict marijuana-related problems.
On the other hand, Helfand, Olsen, and Hillard (2017) found
that FAAH knockout mice exhibited increased active responses
in an operant sensation seeking task. Also, numerous studies
have demonstrated a positive correlation between impulsivity
and sensation seeking, suggesting a common biological
mechanism underlying this association (Hur & Bouchard, 1997).
It is reasonable, then, to ask whether impulsivity and sensation
seeking operate as endophenotypes between FAAH C385A or
rs12075550 and experimental substance use, understanding as
240
such the exploratory behavior during early stages of substance use
(Schindler et al., 2005).
In summary, the objective of this study is to analyze the
associations between three sets of variables: phenotypes of
experimental substance use, genotypes in two variations involved
in the activity of the endocannabinoid system (rs12075550
and C385A SNPs), and two personality traits and potential
endophenotypes (impulsivity and sensation seeking).
Method
Participants
We recruited 929 undergraduate students from the Complutense
University of Madrid. All of them participated voluntarily and a
part received credits for their participation. To reduce the risk of
population stratification, only the data of the 861 participants of
self-reported European ancestry (76.00% female) were analyzed.
Their age ranged from 18 to 40 (M = 20.66, SD = 3.28). They all
filled a consumption questionnaire and donated a saliva sample.
In addition, 591 of them (77.30% female, mean age = 20.09, SD
= 2.78) completed the personality tests. The rest of participants (n
= 270, 73.00 % female, mean age = 21.91, SD = 3.88) did not fill
these tests, because their application was mistakenly omitted.
Instruments
Three different self-report questionnaires were used. An ad
hoc questionnaire on substance use asked the participant, among
other things, whether or not he/she had ever tried alcohol, tobacco,
cannabis, cocaine or synthetic drugs (ever tried), the age of first
use of each of these substances (age of first use), and which of
them he/she had consumed in the past 30 days (currently use).
To assess impulsivity, the Spanish version of the Barrat
Impulsiveness Scale-11A, translated and adapted by Oquendo
et al. (2001), was administered. The BIS-11 is a self-report
questionnaire widely used (Stanford et al., 2009) that contains
30 items, measured on a four-point Likert-type scale. Since the
Spanish version of Oquendo et al. (2001) was based on an initial
version of BIS-11 [BIS-11A] (Barrat, 1994) and with the aim of
making the data comparable to those of studies carried out with
the much more used final version [BIS-11] (Patton, Stanford, &
Barrat, 1995), only the 24 items common to the two versions have
been taken into account (International Society for Research on
Impulsivity, 2013). However, the total scores were transformed
to the usual scale of 30 to 120 points of this final version by
multiplying each of them by 1.25. In this study, Cronbach’s alpha
coefficient for the questionnaire was 0.75.
To assess sensation-seeking, the Spanish version of the
Sensation-Seeking Scale Form V (SSS-V) (Zuckerman, Eysenck,
& Eysenck, 1978), translated and adapted by Perez and Torrubia
(Pérez & Torrubia, 1986), was used. The SSS contains 40 yes-
no items. The items 10, 11, 14, 23 and 39 were not counted,
because they directly ask about the consumption of substances,
which would increase the association of sensation seeking with
consumption, but the total scores were transformed to the usual
scale of 0 to 40 points by multiplying each of them by 1.143. In
this study, Cronbach’s alpha coefficient for the questionnaire was
0.73. The correlation between SSS-V and BIS-11 total scores was
r = .314 (p <.001).
 Associations between experimental substance use, FAAH-gene variations, impulsivity and sensation seeking

Procedure
Participants first signed two informed consents, one for the
collection and use of the data from the questionnaires, and another
for the genetic study. They then completed the questionnaires
and subsequently donated a saliva sample. The Research Ethics
Committee of the Complutense University of Madrid (Faculty of
Psychology) approved all procedures.
DNA from saliva was genotyped as previously described
by Bühler et al. (2014) and Huertas, Bühler, Echeverry-Alzate,
Giménez, and López-Moreno (2012). Briefly, DNA was collected
using Oragene DNA Self-Collection kit (DNA Genotek, Ottawa,
Ontario, Canada) and purified from 250-μl aliquots using the
ethanol precipitation protocol as described by the manufacturer.
TaqMan genotyping was performed using pre-designed and
validated TaqMan SNP genotyping assays (Assay ID: rs324420
and rs1275550) for humans from Applied Biosystems (Foster City,
CA94404, USA). These genotyping assays were performed with a
LightCycler 480II-machine (Roche Diagnostics, Barcelona, Spain)
with endpoint genotyping method. Color fluorescence measures
after amplification were analyzed with LightCycler 480 endpoint
genotyping software version 1.5 (Roche Diagnostics, Barcelona,
Spain).
(CC/CT vs. TT), and for the A allele of FAAH C385A (AA/AC
vs. CC).
Statistical analysis was performed using the Statistical Package
for the Social Sciences of International Business Machines (IBM
SPSS Statistics 22 for Windows, SPSS Inc., Chicago, IL). To test
the association between each of these SNPs with the ever tried and
currently used variables, we used Pearson’s chi-square (χ2) with
exact significance and the odds ratio (OR, 95%IC), controlling
the gender effect by means of the Mantel-Haenszel method.
Survival analysis, estimated by the Kaplan-Meier method, was
used to assess the association of each SNP with age of first use,
and the curves of the genotypes were compared using the Breslow
(Generalized Wilcoxon) test.
To assess the association between ever tried / currently used
of each substance, as well as each SNP, with the BIS-11 / SSS-V
total scores, univariate ANOVAs were used, adding gender as an
additional factor (see e.g. Baker & Yardley, 2002). The Pearson’s
correlation test (r) was applied to measure the strength of the
associations between age of first use and the BIS-11 / SSS-V total
scores.
We applied the Benjamini-Hochberg correction for multiple
tests (Benjamini & Hochberg, 1995), with a false discovery rate
of .05.

Data analysis Results

Data regarding the current use of cocaine and synthetic
drugs were excluded from the analysis because the number of
participants who had consumed these substances in the last 30
days was small (10 and 12 respectively). Consequently, some n per
group were too small when analyzing differences in personality
or differences in genotypes between participants who have
consumed the substances and those who did not. In the same way,
the age at which these two substances were first used was also
excluded because the number of participants who had ever tried
them was small (51 and 59 respectively) and also because this
number was very unbalanced between genotypes. This resulted
in some n per cell too small when comparing ages in function of
genotypes.
Consistent with previous studies (i.e. Bühler et al., 2014) and
after a preliminary data inspection, analysis were performed
under a dominant genetic model for the C allele of rs12075550
Genetic data
Genotype distribution data of both SNPs are shown in Table 1.
The genotype distributions of both SNPs did not deviate from
Hardy-Weinberg equilibrium (FAAH C385A χ2 = 0.32, p = 0.57,
rs12075550 χ2 = 1.96, p = 0.16) neither were there significant
differences between genotypes in the gender distribution
(C385A χ2 = 2.96, p = 0.23, rs12075550 χ2 = 0.12, p = 0.94). Allele
frequency distributions of C385A and rs12075550 were consistent
with the NIH LDlink data for European population, where the
minor allele frequencies were A (21%) and C (41,3%) respectively
(Michiela & Chanock, 2015). In the same way, the distribution of
C385A-rs12075550 haplotype frequency, also shown in Table 1,
was consistent with NIH LDlink data for European population.
The p-values of associations between consumption, genotypes
and personality traits are summarized in Table 2.

Table 1
FAAH C385A and rs12075550 SNPs genotype distribution

Male Female Total Male Female Total Male Female Total

C385A

AA AC CC TOTAL

n 12 23 35 57 207 264 138 424 562 861

% 1,39 2,67 4,07 6,62 24,04 30,66 16.03 49,25 65,27 100

rs12075550

CC CT TT TOTAL

n 43 130 173 95 308 403 69 216 285 861

% 4.99 15,10 20,1 11.03 35.77 46,81 8,01 25.09 33.10 100

Note: Minor allele frequency: 385A = .19; rs12075550 C = .44. Haplotype distribution (C385A - rs12075550): A-C = 0 (0.0%); A-T = 334 (19.4%); C-C = 749 (43.5%); C-T = 639 (37.1%)

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 Evelio Huertas, José A. López-Moreno, Vanessa Fernández, Víctor Echeverry-Alzate, and Kora-M Bühler

Table 2
Association genotypes - consumption
P-value of significant associations between experimental substance use,
personality traits and SNPs, after Benjamini-Hochberg correction for multiple – SNP rs12075550. The percentage of participants who had
tests tried each of the substances was lower among T-homozygotes
Questionnaires SNPs
than among C-allele carriers, but this difference reached
statistical significance only in the case of cannabis (50.18 %
SSS-V BIS-11 C385A rs12075550 vs 57.64 %, χ2 = 4.294, p = .023, odds ratio = 1. 359, p = .036,
95% CI [1.020-1.811]) and synthetic drugs (4.56 % vs 8.85
Substance use
%, χ2 = 5.106, p = .015, odds ratio = 2.046, p = .025, 95%
Ever tried:
alcohol < .001 – – – CI [1.094-3.829]), after applying the Benjamini-Hochberg
tobacco < .001 < .001 – – correction for multiple tests. The T homozygotes were also
cannabis < .001 .001 – .023 significantly older when they first used cannabis (16.6 years
synthetic drugs < .001 - – .015 vs 16.2 years, Breslow χ2 = 5.667, p = .017) and were less
cocaine – .019 – –
likely to be current tobacco users (26.32 % vs 34.90 %, χ2 =
Age of first use: 6.444, p = .011, odds ratio = 1.501, p = .011, 95% CI [1.096-
alcohol <.001 <.001 – – 2.055]).
tobacco – – – –
cannabis <.001 .002 – .017
– SNP FAAH C385A. No consumption phenotype was
significantly associated with this SNP after applying the
Current use:
Benjamini-Hochberg correction for multiple tests.
alcohol < .001 < .001 – –
tobacco .001 < .001 – .011
cannabis < .001 < .001 – – Association genotypes - impulsivity/sensation seeking
SNPs:
C385A – – No significant differences were found between genotypes of
< .001 < .001
rs12075550 – – FAAH C385A or rs12075550 in impulsivity or sensation-seeking.
Questionnaires:
SSS-V – – Discussion
<.001 <.001
BIS-11 – –
In this study, we found for the first time an association of
Note: The results of the specific statistical analyses for each association can be found in
the Results section. Current use indicates whether or not the participant has consumed the experimental substance use with the rs12075550 SNP, but we
substance in the last 30 days could not find that same association with the C385A SNP. We
also found an association of experimental substance use with
impulsivity and sensation seeking. However, we failed to found
Association consumption - impulsivity/sensation seeking an association between any of these genetic variations and any of
those personality traits.
– BIS-11 questionnaire. BIS-11 total scores were higher in The rs12075550 is a genetic variation practically unknown in
participants who have ever tried tobacco (dif = 4.20, F(1, 585) terms of its biochemical background or its phenotypic effects. To
= 16.516, p < .001, partial η2 = .027), cannabis (dif = 3.79, our knowledge, only three studies have included it. In one of them,
F(1, 585) = 10.302, p = .001, partial η2 = .017) or cocaine (dif Flanagan et al. (2006) found that the A allele of FAAH C385A
= 5.10, F(1, 585) = 5.521, p = .019, partial η2 = .009). BIS-11 was associated with the T allele of rs12075550 in up to 92.6%
total scores were also higher in participants with a current use of Caucasian individuals and in 75.2% of African-American
of alcohol (dif = 4.81, F(1, 585) = 14.657, p < .001, partial η2 = subjects using multiple substances. They proposed a haplotype
.024), tobacco (dif = 4.48, F(1,585) = 15.323, p < .001, partial that contains both SNPs. Given this finding, it could be thought
η2 = .026) or cannabis (dif = 4.66, F(1, 585) = 18.087, p < .001, that in our case the association of rs12075550 with experimental
partial η2 = .030). In addition, a negative correlation was found substance use might simply be a result of its association with
between the BIS-11 total scores and age of first use of alcohol C385A, since this SNP has been related to different phenotypes of
(r = -.135, p = .002) or cannabis (r = -.158, p = .002). substance use (e.g. Bühler et al., 2014; Sipe et al., 2002). However,
– SSS-V questionnaire. As expected, SSS-V total scores were in the present study the A allele of FAAH C385A was associated
higher in participants who have ever tried alcohol (dif = with the T allele of rs12075550 in 100% of cases, as correspond to
5.37, F(1, 587) = 16.365, p < .001, partial η2 = .027), tobacco the sample of participants from European ancestry, but also the C
(dif = 2.04, F(1, 587) = 12.777, p < .001, partial η2 = .021), allele of C385A was associated with the T allele of rs12075550 in
cannabis (dif = 2.96, F(1, 587) = 26.778, p < .001, partial η2 46% of cases. This is consistent with the LD haplotype calculation
= .044) or synthetic drugs (dif = 3.93, F(1, 587) = 13.299, for the Iberian population in Spain (Machiela & Chanock, 2015).
p < .001, partial η2 = .022). SSS-V total scores were also These results, together with the lack of association between
higher in those participants who currently use alcohol (dif = FAAH C385A and the consumption variables analyzed in this
2.67, F(1, 587) = 16.165, p < .001, partial η2 = .027), tobacco study, seem to indicate that the association between rs12075550
(dif = 1.78, F(1, 587) = 12.107, p = .001, partial η2 = .020) and experimental substance use would not be a consequence of its
or cannabis (dif = 3.24, F(1, 586) = 31.162, p < .001, partial linkage disequilibrium with FAAH C385A.
η2 = .050). We also found a negative correlation between In a second study involving rs12075550, Bühler et al. (2014)
SSS-V total scores and age of first use of alcohol (r = -.208, failed to found an association between this SNP and intensity of
p <.001) or cannabis (r = -.178, p <.001). alcohol, tobacco or cannabis consumption. However, the results

242
 Associations between experimental substance use, FAAH-gene variations, impulsivity and sensation seeking
of the present study indicate that it may be associated with
having ever tried some substances, with the age at which they
were first used and with having used them in the last 30 days.
That is, the TT genotype of this SNP could confer a protective
effect against experimental substance use. Since this type of use
and risk consumption are partially independent (e.g. Swendsen et
al., 2012), this SNP may be related to the first type of use, but not
necessary to the second.
To our knowledge, only one study has so far explored the
biochemical implications of rs12075550, demonstrating that it is
likely to affect protein binding and FAAH gene expression, as
demonstrated in lymphoblastoid cell lines (Veyrieras et al., 2008).
However, any functional explanation of the association we have
found between this SNP and phenotypes related to experimental
substance use would be scarcely justified at the current level of
knowledge.
With respect to FAAH C385A, its behavioral consequences in
human substance use are still under research (Bühler et al., 2015).
The results obtained in this work have not shown a statistically
significant association between FAAH C385A and the phenotypes
under study, so the effect of this SNP could be more directly
related to substance use disorders, which is what has usually been
explored, than to experimental substance use.
Extensive empirical evidence indicates that impulsivity and
sensation seeking are personality traits associated with substance
consumption, particularly in earlier stages of substance use (e.g.
Meil et al., 2016; Michell & Potenza, 2014; Moreno et al., 2012).
Some studies indicate that substance use increases impulsivity
and sensation seeking (e. g. de Wit, 2009; Ersche et al., 2010).
However, other studies with both humans (e.g. Farley & Kim-
Spoom, 2015; Fernández-Atarmendi, Martínez-Loredo, Grande-
Gosende, Simpson, & Fernández-Hermida, 2018) and animals
(e.g. Belin, Mar, Dalley, Robbins, & Everitt, 2008; Diergaarde
et al., 2008) also indicate that impulsivity and sensation seeking
increase substance use. Since impulsivity and sensation seeking
have been related to the endocannabinoid system (e.g. Helfandet
al., 2017; Moreira, Jupp, Belin, & Dalley, 2015; Ucha et al.,
2019) they were suitable candidates as endophenotypes between
the FAAH gene variations and the phenotypes of experimental
substance use analyzed in this study. To our knowledge, there
are no previously published data on the association between
rs1275550 and impulsivity or sensation seeking, but with respect
to the association of C385A with impulsivity, previous studies
have obtained contradictory results (Bidwell et al., 2013; Hariri
et al., 2009). In the present study we failed to found a significant
association between either of the two SNPs and neither of the
two personality variables, although our data show an association
References
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between these personality variables and experimental substance
use on the one hand, and between rs1275550 and some phenotypes
of that experimental use on the other. Therefore, it does not seem
that impulsivity or sensation seeking, closely related to each other
according to our and previous results, operate as endophenotypes
between any of the two SNPs and the phenotypes of substance use
that we have analyzed.
One limitation of the present study is its exploratory nature.
For this reason, three variables related to the experimental use
of each of five substances, two personality traits and two SNPs
related to the FAAH gene were included. And for this same reason
the Benjamini-Hochberg correction for multiple tests was applied.
Another limitation is that participants constitute a convenience
sample, composed of university students of European ancestry,
mostly female. Therefore, the data are not directly generalizable to
other populations. Particularly important is that participants were
not recruited on the basis of their substance use. Consequently,
any generalization to this type of patients should be done with
caution. A last limitation is related to the fact that the impulsivity
and sensation seeking questionnaires were applied to only 591 of
the 861 participants, as indicated in the Participants section, so
the conclusions regarding these variables should be interpreted
according to that smaller number. The results obtained here will
therefore have to be replicated through further studies before
drawing definitive conclusions.
In conclusion, we provide first evidence for an association between
SNP rs12075550 and phenotypes of experimental substance use. On
the other hand, consistently with previous evidence, we found that
impulsivity and sensation seeking are associated with these same
phenotypes in our sample of young people of European ancestry,
although our data do not permit to establish causal relationships.
Nevertheless we failed to found a significant association of
rs12075550 or FAAH C385A SNPs with one or another personality
trait. In any case, these results show the importance that genetic
and personality differences have in the experimental substance
use and in the probability of developing a substance use disorder
as a consequence of that use. They also highlight the importance
of taking into account these individual differences, together with
contextual factors, when designing prevention policies.
Acknowledgements
This work was supported by Fondo de Investigación Sanitaria
- Red de Trastornos Adictivos - FEDER (RD16/0017/0008),
Ministerio de Economía y Competitividad (PEJ-2014-A-17012-C)
and Ministerio de Sanidad, Consumo y Bienestar Social - Plan
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